Limited effects of m⁶A modification on mRNA partitioning into stress granules.

ABSTRACT: The presence of the m⁶A modification in mammalian mRNAs is proposed to promote mRNA recruitment to stress granules through the interaction with YTHDF proteins. We test this possibility by examining the accumulation of mRNAs in stress granules in both WT and ∆METTL3 mES cells, which are deficient in m⁶A modification. A critical observation is that all m⁶A modified mRNAs partition similarly into stress granules in both wild-type and m⁶A-deficient cells by single-molecule FISH. Moreover, multiple linear regression analysis indicates m⁶A modification explains only 6% of the variance in stress granule localization when controlled for length. Finally, the artificial tethering of 25 YTHDF proteins on reporter mRNAs leads to only a modest increase in mRNA partitioning to stress granules. Since most mammalian mRNAs have 4 or fewer m⁶A sites, and those sites are not fully modified, this argues m⁶A modifications are unlikely to play a significant role in recruiting mRNAs to stress granules. Taken together, these observations argue that m⁶A modifications play a minimal, if any, role in mRNA partitioning into stress granules.

SUBMITTER: Khong A 

PROVIDER: S-EPMC9243116 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature